JDIT 2014 0620 001.pdf

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Journal of Diagnostic Imaging in Therapy. 2014; 1(1): 1-19

Grachev et al.

time zero by calculating p1 + p3 from the estimated parameters of the POB (t) model function agreed
with the ratio 1  H . Over the first 30 minutes of the scan, the plasma-over-blood activity ratio
decreased. At later times the plasma-over-blood activity ratio rose again, consistent with the
appearance of polar radiolabelled metabolites in the blood plasma.

Figure 2. Time courses of the ratio of the plasma activity concentration over the whole
blood activity concentration (A) and of the fraction of parent 11C-SCH442416 in plasma
(B) for the four subjects. The circles mark the measured data points, the dashed lines
represent the fitted curves. Note the change of the sampling protocol from 5, 10, 15, 20, 30,
40, 50, 60, 75 and 95 minutes in subjects 1 and 2 to 3, 7, 11, 15, 20, 30, 45, 60, 75 and 95
min in subjects 3 and 4 to account for the faster metabolism of 11C-SCH442415 in humans
than reported in animals.
The radiochromatograms of the plasma radioactivity showed a minor polar radioactive component
(retention time about 4.2 min) and a main component (retention time of 7.5 min) which was identified
as 11C-SCH442416 as it co-eluted with the same retention time as the unlabelled authentic standard of
SCH442416. The other radioactive compounds observed in plasma were more polar than 11CSCH442416 but were not identified. The percentage of radioactive metabolites was observed to
increase with time (B). The fraction of unmetabolized parent tracer in blood plasma averaged over the
four subjects decreased from 87% at 3 minutes to about 41% at 15 minutes and 15% at 95 minutes
post-injection, respectively. Therefore, the peripheral metabolism of 11C-SCH442416 is faster in
humans than previously reported in rats [11] and in a macaca nemestrina [13].
3.2. Tissue activity
There was rapid uptake of 11C-SCH442416 in all brain regions. Inspection of the integral PET image
from 1 to 30 minutes after injection reveals that the A2A receptor rich striatal regions show higher
activity than cortical brain areas and the cerebellum.

ISSN: 2057-3782 (Online)